Hydroxychloroquine in ANCA Vasculitis Evaluation - A Multicentre, Randomised, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 43
- 试验地点
- 18
- 主要终点
- The percentage of patients with • uncontrolled AAV disease activity OR • controlled AAV disease activity but prednisolone dose >7.5mg daily OR • controlled AAV disease activity but any corticosteroid use >7.5mg daily for any reason
研究概览
简要总结
The purpose of this study is to find out whether hydroxychloroquine, in addition to background treatments, reduces disease activity in patients with Anti-Neutrophilic Cytoplasmic Autoantibodies (ANCA) Vasculitis, a group of autoimmune diseases.
Hydroxychloroquine and is an established, effective, safe and inexpensive therapy, widely used in other autoimmune diseases such as lupus and rheumatoid arthritis.
The study is open to adults diagnosed with certain types of vasculitis, called Granulomatosis Polyangiitis (GPA), Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA). Participants will be eligible if they are treated with background medication to control their vasculitis disease and have a low level of disease activity as defined by a Birmingham Vasculitis Activity Score (BVAS) of greater than 3.
Participants will be randomly placed in 1 of 2 groups. Both groups will be given background medication. One group will receive hydroxychloroquine and the other will receive placebo. Participants will be on treatment for 1 year.
76 ANCA Vasculitis participants will be recruited (38 in each treatment arm) from UK vasculitis specialist centres.
详细描述
This is a multi-centre, randomised, placebo-controlled, double-blind study to evaluate if hydroxychloroquine in combination with background maintenance therapy improves the clinical response and quality of life in patients with AAV. 76 participants who have Granulomatosis with Polyangiitis, Microscopic Polyangiitis or Eosinophilic Granulomatosis with Polyangiitis will be recruited from 20 sites.
They will be randomised in a 1:1 ratio of hydroxychloroquine or placebo. Neither the patient nor the research team will know which treatment group the participant is in.
Once the participant agrees to take part and has signed informed consent, they will undergo the following assessments, tests and procedures to find out if they can take part in the study. Some may be routinely done by the study doctor as part of regular vasculitis care even if the participants are not in the study:
- Medical history
- Birmingham Vasculitis Activity Score (BVAS)
- Physical exam
- Blood tests
- Pregnancy test
- Urine drug test
- Electrocardiogram
If the patient is eligible to take part in the study, they will be randomised to receive either hydroxychloroquine or placebo in addition to background medication. Participants will receive 2 tablets to take once a day over the course of a year. Participants may have their dose reduced to 1 tablet dependent on their weight at baseline and renal function. All participants will have their prednisolone dose tapered down over the course of the study. Participants will be asked to fill in a patient diary on a weekly basis to record whether they've taken their medication, and if they've experienced any change of symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Central trial pharmacist will be unblinded during trial.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine.
- •Patients with an estimated glomerular filtration rate (eGFR) <30 ml/min.
- •Patients weighing <40kg.
- •Sensitivity, anaphylaxis or allergy to hydroxychloroquine or any other 4-aminoquinoline compound.
- •Known glucose 6 phosphate dehydrogenase deficiency.
- •Known lactose intolerance.
- •Evidence of plaque psoriasis.
- •Concomitant use of the following medications within the last six months:
- •Tumour necrosis factor inhibitor treatment (e.g. etanercept) Cyclophosphamide Abatacept Alemtuzumab Any experimental biological therapies Intravenous, intramuscular or sub-cutaneous immunoglobin Plasma exchange Antithymocyte globulin Tamoxifen Live vaccines
- •B cell depleting therapy (rituximab) for remission induction within the last six months. Rituximab maintenance therapy is permitted.
- •Severe or rapidly progressive ANCA vasculitis with at least one major BVAS item.
- •Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to vasculitis (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious disease) which, in the opinion of the principal investigator, could confound the results of the study or put the patient at undue risk.
- •Patients taking long term macrolide antibiotics for a chronic condition. This does not include topical preparations.
- •Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
- •Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to randomisation. A urine drug screen should be performed and confirmed negative prior to study entry.
- •Have a historically positive test or test positive at screening for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody or are known to be HIV-1 positive.
- •Have a Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale (version 5), unless considered by the investigator to be related to the underlying disease or induction therapy.
- •Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results, including: - QT interval corrected using the same consistent formula at each visit (QTc) > 470 msec for female > 450 msec for male patients demonstrated by at least two ECGs.
- •Participation in any other interventional trial within the last 6 months.
- •Have a current symptomatic COVID-19 infection.
- •Have been admitted to the ICU in the past 6 months due to a COVID-19 infection.
研究组 & 干预措施
Hydroxychloroquine
Patients will be receive 400mg of Hydroxychloroquine (2 x 200mg) to take daily for 52 weeks. Hydroxychloroquine will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg.
Patients weighing <50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.
干预措施: Hydroxychloroquine (Drug)
Placebo
Patients will be receive 400mg of Placebo (2 x 200mg) to take daily for 52 weeks. Placebo will be started at a dose of 200mg an up-titrated after the first week to a maximum daily dose of 400mg.
Patients weighing <50kg, or those patients with an eGFR of 30-50mL/min, will receive a reduced dose of 200mg daily.
干预措施: Placebo (Drug)
结局指标
主要结局
The percentage of patients with • uncontrolled AAV disease activity OR • controlled AAV disease activity but prednisolone dose >7.5mg daily OR • controlled AAV disease activity but any corticosteroid use >7.5mg daily for any reason
时间窗: BVAS will be assessed during the final 12 (±7 days) weeks that the patient is on the study drug in the trial.
The primary endpoint will be the percentage of patients with: EITHER * uncontrolled AAV disease activity (defined as BVAS \> 3) OR * controlled AAV disease activity (BVAS ≤ 3) but prednisolone dose \>7.5mg daily OR * controlled AAV disease activity (BVAS ≤ 3) but any corticosteroid use \>7.5mg daily for any reason at any point during the final 12 weeks (±7 days) of the study. Inhaled corticosteroids will not contribute to the primary endpoint, nor will methylprednisolone given for rituximab maintenance therapy.
次要结局
- Total number of infections per patient(From date of randomisation through to week 56 follow up)
- Time to remission(From date of randomisation through to week 56 follow up)
- Time to first severe flare(From date of randomisation through to week 56 follow up)
- Proportion of patients categorized as having a severe flare at each of the time points in the trial schedule excluding screening, baseline and week 56(Weeks 1-52 excluding screening, baseline and week 56)
- Proportion of patients with treatment failure at week 52(Week 52)
- Cumulative prednisolone dosage(From date of randomisation through to week 56 follow up)
- Total number of vasculitis flares (severe and limited) per patient(From date of randomisation through to week 56 follow up)
- Time to first limited flare(From date of randomisation through to week 56 follow up)
- Total number of adverse events(From date of randomisation through to week 56 follow up)
- Absolute values and relative change from baseline in the Vasculitis Damage Index (VDI) at each time point outlined in the trial schedule.(From date of randomisation through to week 56 follow up)
- Proportion of patients categorized as having a limited flare at each of the time points in the trial schedule excluding screening, baseline and week 56(Weeks 1-52 excluding screening, baseline and week 56)
- Cumulative number of visits BVAS = 0(Week 4 through to week 52)